Autoantibodies to nuclear antigens are present in the sera of patients with certain systemic rheumatic diseases. This research plan proposes to use two main approaches for studying these antinuclear antibodies. The first is to characterize the immunochemistry of the nuclear antigens and if possible isolate these antigens for chemical and biological studies. The second approach is to determine the clinical significance of these antinuclear antibodies. To achieve the first objective, we shall apply physico-chemical as well as immunological methods to isolate and purify nuclear antigens. The physico-chemical methods will include adsorption chromatography, gel filtration and isoelectric focusing. For the immunological methods, we shall use IgG antinuclear antibodies from patients as immunoadsorbants to isolate the homologous nuclear antigen. In both these methods, the objective will be to isolate the antigen in as homogenous a state as possible, for chemical and biological studies. Attempts will be made to characterize profiles of antinuclear antibodies in systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome and progressive systemic sclerosis. A major undertaking will be the detection of immune complexes consisting of nuclear antigens and antibody in the sera of such patients and determination of their pathogenetic potential. Participation of complement activation by these immune complexes in the causation of tissue injury will be studied by assays for immune complexes with the Clq deviation technique and a correlation of the latter findings with the presence of complement split products in plasma and serum.